Cancer therapy prostate

DES was once a mainstay of prostate cancer therapy. While very effective in androgen ablation, DES-treated patients experienced increased cardiovascular mortality.41 LHRH agonists, with equivalent efficacy and decreased cardiovascular toxicity, supplanted DES as a mainstay of therapy. 

Patri, A.K., Myc, A., Beals, J., Thomas, T.P., Bander, N.H., and Baker Jr., J.R. (2004) Synthesis and in vitro testing of J591 antibody-dendrimer conjugates for targeted prostate cancer therapy. Bioconjugate Chem. 15, 1174-1181. 

Flutamide was the first drug used in prostate cancer therapy for which the withdrawal syndrome was reported. In that study, 40% of patients showed a decline in prostate specific antigen (PSA) levels after cessation of flutamide from the therapeutic protocol. The decline in PSA levels was associated with an improvement of the clinical symptoms. Based on these paradoxical observations, the concept of sequenced androgen ablation was proposed [217]. Several phase II clinical studies were performed, demonstrating safety and tolerability, however, a direct comparison in randomised phase III trials is necessary [218]. 

An initial flare in bone pain may occur (prostate cancer therapy)... 

Fast neutrons were the first nonconventional radiation used in cancer therapy. Fast neutrons (a high-LET radiation) were introduced for the following radiobiological reasons (1) a reduction of the OER with increasing LET (2) a reduction in the difference in radiosensitivity related to the position of the cells in the mitotic cycle (3) and less repair and thus less clinical relevance of the different repair mechanisms. The best and clinically proven indications for fast neutrons are salivary gland tumors, locally advanced prostatic adenocarcinomas, and slowly growing, well-differentiated sarcomas. 

Fishman P, Bar-Yehuda S, Rath-Wolfson L, Ardon E, Barrer F, Ochaion A, Madi L (2003) Targeting the A3 adenosine receptor for cancer therapy inhibition of prostate carcinoma cell growth by A3AR agonist. Anticancer Res 23(3A) 2077-2083 Fishman P, Bar-Yehuda S (2003) Pharmacology and therapeutic applications of A3 receptor subtype. Curr Top Med Chem 3(4) 463 169... 

Most steroid-sensitive cancers express specific cell surface receptors. Prednisone-sensitive lymphomas, estrogen-sensitive breast cancers, and prostatic cancers express specific receptors for corticosteroids, estrogens, and androgens, respectively. It is now possible to assay tumor specimens for steroid receptor content and to identify which individual patients are likely to benefit from hormonal therapy. Measurement of the estrogen receptor (ER) and progesterone receptor (PR) proteins in breast cancer tissue is now standard clinical practice. ER or PR positivity predicts response to hormonal therapy, whereas patients whose tumors are ER-negative generally fail to respond to such treatment. 

Yu DC, Sakamoto GT, Henderson DR. Identification of the transcriptional regulatory sequences of human kallikrein 2 and their use in the construction of calydon virus 764, an attenuated replication competent adenovirus for prostate cancer therapy. Cancer Res 1999 59 1498-1504. 

We and others have demonstrated that Raf-1 protein serine/threonine kinase is a druggable signaling molecule in cancer therapy (1,13,17,21-25). Our laboratory has developed a novel cationic liposomal formulation for systemic delivery of intact raf ASO (LErafAON) to normal and tumor tissues in mice (13,17). The liposome-entrapped raf antisense oligonucleotide (LErafAON) is also the first liposomal ASO drug tested in humans (26,27). Systemically delivered cationic liposomal nanoparticles containing rafsiRNA (LErafsiRNA) also inhibit Raf-1 protein expression in tumor and most normal tissues in human prostate tumor (PC-3)-bearing athymic mice (Fig. 1 and Color Plate 1, see Color Plate Section). 

Salvage therapy for breast cancer and prostate cancer... 

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